505(b)(2)s and Women’s Health Issues

By Edward Allera

By using the 505(b)(2) new drug application pathway, sponsors can add value to already approved drugs through calculated steps. New technology, old data, and literature can create sophisticated, novel endpoints. With these pieces, a company can obtain new and improved labeling, market exclusivity, and even patent protection for women’s health products. Recent FDA/CDER actions have created the most conducive environment for approving women’s health products ever.  It is not necessary to start from square one to produce profit in the women’s health space. However, it is important to listen, think, and be interactive. The environment that led to the boom in oncology products is being replicated for women’s health.

1. Background

According to CitiGroup and others, only approximately 4% of health care investment dollars goes to women’s health, yet women account for more than half of the U.S. population. Women are the primary care givers, and according to the Illuminators they make more than 70% of the healthcare spending decisions. Moreover, the pandemic opened the window to active discussion of women’s health issues.  A prime market exists, but how can a company capitalize on this market?

1.  Building Trust

In today’s health care marketplace, “trust” is the rarest commodity. Creating a reputation for trust, integrity, and leadership in specific woman’s health areas can be accomplished in the dynamic regulatory environment that is evolving. With 505(b)(2) applications, a company starts with a drug that has already been shown to be safe and effective, which provides some comfort to potential patients. FDA, NIH (including the National Cancer Institute), and others are publicly committed to expanding clinical trial research and product development in diverse populations, especially women. Why? Because the original approvals were based on data from refined patient groups. Expanding on this effort, FDA has recently issued guidelines that fit perfectly into this environment for women’s health products: conducting decentralized clinical trials, real world evidence considerations for non-invasive clinical trials, and drug delivery output for medical devices. These steps are designed to ensure that approved products are optimally effective in the real world. They can also be relevant to reducing overall health care costs.

1. A New Forum for Dialogue

CDER has over twenty reviewing divisions, and each reviewing division has its own history, precedents, and requirements. Many deal with women’s health issues. Before approaching that reviewing division, it is critical to review that division’s history. The look, listen, and link with new technology approach can work for products in a reviewing division, but the obvious limitations of those divisions led to creation of a new forum. In April 2024, FDA created the CDER Center for Clinical Trial Innovation (C3TI) to attempt to replicate the success of the Office of Oncology Excellence (OOE). Over the past decade, most advances in innovative clinical trials and measurement of clinical benefit have arisen from the OOE. These advances have led to the boom in oncology research and revenue for approved oncology drug products.
C3TI is open for business and will be open minded, as the Federal Register notice announcing its creation states. It is seeking comments from, and dialogue with, industry. Working with this Center to facilitate women’s health product development can help a company establish its bona fides as a thoughtful and creative new player in the women’s health space. You can become a known, reputable commodity in a less crowded field—an invaluable first step.

1. Creating the Dialogue

What do you discuss with C3TI? Because C3TI is in its infancy, it will be looking to learn from industry. A sponsor that listens to women’s needs and concerns for new products provides that company, and C3TI, with invaluable information. That information will help the Center grow and innovate, which is another vital step in building the trust that will pay multiple financial returns.
This approach can also help improve existing treatments and therapies for conditions that only, or disproportionately, affect women or that affect women differently than men. Many of these existing treatments are dated. Many are based on data extrapolations due to the absence, or dearth, of women in the original clinical trials. Literature and medical education may be the only source of information for others.
Further, the signs and symptoms of menopause, perimenopause, and a number of other women’s conditions are not well known and seldom discussed among clinicians let alone patients. Women are often told by clinicians that their symptoms only exist in their heads.

1. Linking the Technology

New technologies, such as artificial intelligence (AI), that can optimize drug delivery, therapy maintenance, and diagnosis of conventional and orphan indications abound. These technologies can mine data for new signs, symptoms, biomarkers, and surrogate endpoints to provide more refined definitions of classical endpoints, diagnosis, and monitoring. Further, AI technology is increasing the rate and ability to identify relevant previously unknown linkages to women’s health conditions.
These technologies can identify new or better endpoints that can refine labeling to permit promotion of safer and better pharmaceuticals that are eligible for market exclusivities. Furthermore, a solid patent strategy can result in listing patents in FDA’s Orange Book. These value-added medicines may also be considered sole source products that can avoid generic reimbursement rates.

1. FDA has Issued Guidelines to Aid and Accelerate the Linkages

Modest technologic changes led to shifts from multiple daily dosing of oral tablets to extended-release daily dosing and topical patches. Improved technology has also led to various new aerosol dosage forms and sophisticated injections. Those technologies created new markets, industries, and innumerable products introduced to the market via the 505(b)(2) and other historical regulatory pathways. All were built on known clinical end points. Those old technologies pale in comparison to the technologic breakthroughs that are being created today that can link endpoints.

1. Next Steps

The 505(b)(2) Platform has a tool, Navicen, to accelerate the identification and development of these value-added products. Of course, thought and planning are required for identifying the right entry point at FDA and creating the dialogue.
On Wednesday, October 23, 2024, Value Added Medicines Week will focus programming exclusively on women’s health issues. This forum will provide additional insight into development of products for women’s health. We hope you will join Platform and Value-Added Medicines Week.